Plasma Exchange Treatment Research Articles

Ineffectiveness of therapeutic plasma exchange as a last resort in severe COVID-19 cases: Experience from a tertiary intensive care unit.

Several studies have suggested that cytokine release syndrome (CRS) can be controlled by therapeutic plasma exchange (TPE) treatment. In this study, it was aimed to evaluate the efficacy of TPE treatment in patients who developed life-threatening respiratory failure syndrome (SARS) due to COVID-19 infection. In this retrospective, case-control study, patients, who developed SARS, were infected with the COVID-19 virus, and required intensive care unit (ICU) admission were included. Patients included in the study were divided into groups according to whether TPE experience or not and if so, how many sessions were applied. Mortality rates of patients in the ICU and 30-day mortality ratios were evaluated. A total of 110 patients, 71.8% of whom were male, with a mean age of 59.7 ± 13.3 years, were included in our study. It was observed that 70% of the patients died within a month and 80% of them died during the ICU follow-up period. The 30-day mortality rates of patients who underwent TPE at least once and those who never underwent TPE were 72.2% and 67.9%, respectively (p: 0.617). CRP, D-dimer, fibrinogen and platelet levels showed to have a decreasing trend after plasmapheresis and fluctuated thereafter. It was observed that procalcitonin and IL-6 levels were increased in the group that underwent plasmapheresis but decreased in those who did not receive plasmapheresis. Patients severely infected with SARS-CoV-2 showed fluctuations in inflammatory parameters despite TPE treatment; CRS was not suppressed by TPE; and this treatment did not confer survival benefit in this patient group.

Plasma exchange and intravenous immunoglobulin prolonged the survival of a porcine kidney xenograft in a sensitized, deceased human recipient.

The primary limitation to kidney transplantation is organ shortage. Recent progress in gene editing and immunosuppressive regimens has made xenotransplantation with porcine organs a possibility. However, evidence in pig-to-human xenotransplantation remains scarce, and antibody-mediated rejection (AMR) is a major obstacle to clinical applications of xenotransplantation. We conducted a kidney xenotransplantation in a deceased human recipient using a porcine kidney with five gene edits (5GE) on March 25th, 2024 at Xijing Hospital, China. Clinical-grade immunosuppressive regimens were employed, and the observation period lasted 22days. We collected and analyzed the xenograft function, ultrasound findings, sequential protocol biopsies, and immune surveillance of the recipient during the observation. The combination of 5GE in the porcine kidney and clinical-grade immunosuppressive regimens prevented hyperacute rejection. The xenograft kidney underwent delayed graft function in the first week, but urine output increased later and the single xenograft kidney maintained electrolyte and pH homeostasis from postoperative day (POD) 12 to 19. We observed AMR at 24h post-transplantation, due to the presence of pre-existing anti-porcine antibodies and cytotoxicity before transplantation; this AMR persisted throughout the observation period. Plasma exchange and intravenous immunoglobulin treatment mitigated the AMR. We observed activation of latent porcine cytomegalovirus toward the end of the study, which might have contributed to coagulation disorder in the recipient. 5GE and clinical-grade immunosuppressive regimens were sufficient to prevent hyperacute rejection during pig-to-human kidney xenotransplantation. Pre-existing anti-porcine antibodies predisposed the xenograft to AMR. Plasma exchange and intravenous immunoglobulin were safe and effective in the treatment of AMR after kidney xenotransplantation.

Short-term efficiency of plasma exchange in combination with immunosuppressants and/or biologics in the treatment of idiopathic inflammatory myopathy with rapidly progressive interstitial lung disease: a systematic review and meta-analysis

Objective Rapidly progressive interstitial lung disease (RP-ILD) is a frequent and serious manifestation of idiopathic inflammatory myopathy (IIM) associated with poor outcomes. Plasma exchange (PE) can quickly remove pathogenic substances from the blood. Therefore, PE may be efficacious in IIM patients who have elevated levels of autoantibodies, cytokines and chemokines, fighting for time for immunosuppressive therapy. However, the value of adding PE to immunosuppressants remains unclear. The purpose of this study was to determine the short-term outcomes, including the survival rate at 6 months and change of the laboratory data, of PE in combination with immunosuppressants and/or biologics in the treatment of IIM-RP-ILD. Methods We searched PubMed, Embase and Cochrane Library to find reports of interest published from inception to March 4, 2024. STATA 15.1 was used for data analysis. A fixed or random-effects model with inverse-variance weighting was used to estimate the pooled risk ratio (RR) and 95% confidence interval (CI). Results Two hundred and thirty studies were identified. Eleven studies, including five retrospective cohort studies, four case-control studies and two case series, were included. PE was performed on 114 patients. The survival rate at 6 months was 80% (95%CI = 64%–92%), with moderate heterogeneity (I 2=63.45%, p < 0.05). Moreover, the 6-month survival rate was significantly better in the PE group than in the non-PE group (RR, 1.34; 95% CI = 1.05–1.71, I 2=30.7%; p = 0.194). ILD-related serum markers, including ferritin, KL-6 and anti-MDA-5 antibody titres, were significantly suppressed by a series of PE treatments (p < 0.05). Conclusion The application of PE therapy plus treatment with corticosteroids, immunosuppressants and/or biologics was effective for patients with IIM-RP-ILD. PE may have additional supportive effect in intractable disease.

Plasma exchange does not improve overall survival in patients with acute liver failure in a real world cohort

Background and AimsTherapeutic plasma exchange (PEX) has emerged as a potential treatment option for patients with acute liver failure (ALF). The effect of PEX on survival outcomes outside of clinical trials is not yet well established. In this study we aimed to evaluate the real-world use and outcomes of PEX for the treatment of ALF. MethodsThis multicentre retrospective cohort study included consecutive patients with ALF admitted to all 7 tertiary liver transplant centres in the United Kingdom (UK) between June 2013 and December 2021. Changes in clinical variables following PEX treatment was assessed and overall survival and transplant free survival (TFS) to hospital discharge of patients receiving PEX were compared to those receiving standard medical therapy (SMT). Propensity score matching was performed to control for intergroup covariates and selection bias. ResultsWe included 378 patients with ALF (median (IQR) age 36 (28-48), 64% (n=242) female) of which 120 received PEX. There was a significant improvement in most clinical variables following PEX, including median dose of noradrenaline (reduction from 0.35 μg/kg/min (0.19 - 0.70 μg/kg/min) to 0.16 μg/kg/min (0.08 - 0.49) (p = 0.001). There was no significant difference between PEX and SMT groups in overall survival (51.4 % v 62.6 % respectively, p = 0.12) or TFS (42.6 % v 53.1 %, p = 0.24). ConclusionPEX is now frequently used in the management of ALF patients in the UK. It is associated with significant improvement in haemodynamic parameters but there is no survival benefit. Impact and implicationsPEX is frequently used in the management of patients with ALF in the UK. This real-world study demonstrates significant improvement in haemodynamic status but has not confirmed the survival benefit seen in previous published literature. These results should help inform future use of PEX.

Decreased NETosis-related regulators in neuromyelitis optica spectrum disorders after plasma exchange

ObjectivesTo investigate the impact of plasma exchange (PLEX) on NETosis-related regulators and their correlation with neurological improvement in NMOSD patients. MethodsTwelve aquaporin-4 antibodies seropositive NMOSD patients were enrolled. NETosis-related regulators (myeloperoxidase [MPO], citrullinated histone H3 [CIT-H3], peptidyl arginine deiminase 4 [PAD4], neutrophil elastase [NE], CD64), pro-inflammatory cytokines (IL-1, IL-6, IL-12, TNF-α) and anti-inflammatory cytokines (IL-10, TGF-β1) were quantitatively assessed before and after PLEX treatment. Clinical assessments included expanded disability status scale (EDSS) and visual outcome scale (VOS) scores. ResultsFollowing PLEX, all patients showed symptom improvement, with 66.7 % achieving marked-to-moderate improvement (MMI) at 3 months. Key regulators, such as MPO, CIT-H3, PAD4, NE, and pro-inflammatory cytokines such as IL-1, IL-6, IL-12, and TNF-α, exhibited a statistically significant decrease immediately after the initial PLEX session (P < 0.05). Furthermore, CD64 levels demonstrated a substantial decline after the second PLEX session (P < 0.05). Conversely, the levels of anti-inflammatory cytokines, including IL-10 and TGF-β1, displayed an ascending trend post-PLEX. In clinical relevance analysis, among patients who reached MMI, the reductions in MPO, IL-1, and IL-6 exhibited statistically significant differences when compared to patients in the mild-to-no improvement group (P < 0.05). Pearson correlation analysis revealed that the percentage reduction in IL-6 levels after PLEX was positively correlated with the percentage reduction in patient EDSS/VOS scores (r = 0.638, P < 0.05). ConclusionsThis study highlights that reduced levels of NETosis-related regulators after PLEX contribute to clinical improvement, suggesting the potential involvement of NETosis in the acute neurological impairment observed in NMOSD.

Clinical features of anti-neurofascin-155 antibody positive autoimmune nodopathy in 6 children

Objective: To analyze the clinical features of anti-neurofascin-155 (NF155) antibody positive autoimmune nodopathy in children. Methods: This was a case series study. A total of 6 children who were diagnosed accurately as anti-NF155 antibody positive autoimmune nodopathy by cell immunofluorescence assay at the Children's Hospital of Fudan University from January 2020 to December 2023 were collected. This study retrospectively analyzed 6 pediatric children's clinical manifestations, laboratory and electrophysiological examination results, and treatment outcomes. Results: Among 6 children with anti-NF155 antibody positive autoimmune nodopathy, there were 4 boys and 2 girls. The onset age of 6 children ranged from 3 years and 8 months to 12 years. All 6 children had extremity weakness (more severe in the distal and the lower extremities than in the upper extremities), 5 children had sensory deficits such as numbness or pain in the extremities, 4 children had tremors and ataxia, 3 children had cranial nerve involvement. Among the 6 children, 4 children had protein-cell separation in cerebrospinal fluid examinations. Among the 6 children, 1 child had central nervous system demyelination, the brain magnetic resonance imaging showed multiple abnormal signals in the bilateral cerebral hemispheres. Four children showed motor and sensory nerve damage in electrophysiological examination, and 2 children only showed motor nerve damage. Three children showed myelin and axonal damage, and 3 children only showed axonal damage. Among the 6 children, 5 children were treated with intravenous immunoglobulin and steroids. Among them, 2 children underwent plasma exchange due to poor efficacy, and subsequently, rituximab was added. There was 1 child changed the treatment with olfatomumab since the symptoms did not significantly improve after using rituximab. After treatment for 4-15 months, 2 children had no clinical symptoms, 1 child had improvement in clinical symptoms, 2 children had no significant improvement in clinical symptoms, and 1 child who did not receive the immunotherapy had no significant change in clinical symptoms. Conclusions: Anti-NF155 antibody positive autoimmune nodopathy in children presents with varying degrees of clinical manifestations. It is mainly characterized by extremity weakness, numbness and pain, often accompanied bytremorsand ataxia. Some pediatric patients may also have central nervous system demyelination. Cerebrospinal fluid and electrophysiological examination are important auxiliary examination methods. If steroid therapy is not effective, plasma exchange and rituximab treatment should be used as soon as possible.

On-treatment decline in MELD score predicts one-month transplant-free survival in rodenticidal hepatotoxicity patients treated with low-volume plasma exchange.

Plasma exchange (PLEX) improves survival in patients with rodenticidal hepatotoxicity. However, predictors of treatment response are unknown. We aimed at assessing predictors of response to PLEX treatment in these patients. Patients with rodenticidal hepatotoxicity from 2014 to 2023 managed in our department were included in this study. Kochi criteria (model for end-stage liver disease [MELD] score 36 or international normalized ratio [INR] 6 with hepatic encephalopathy[HE]) derived specifically for rodenticidal hepatotoxicity (PubMed IDentifier [PMID]: 26310868) were used to assess need for liver transplantation. We analyzed predictors of survival at onemonth. ∆Bilirubin, ∆MELD score and ∆INR were calculated as percentage change of the parameter after third PLEX session (or after last PLEX if < 3 PLEX sessions done) from baseline pre-PLEX value. Of 200 patients with rodenticidal hepatotoxicity, 114 patients were treated with low-volume PLEX (PLEX-LV). No patient had liver transplantation. Of 78 patients who fulfilled Kochi criteria, 32 patients were PLEX-LV eligible and underwent PLEX-LV (M: 10; age: 20.5, 7-70years; median, range; acute liver failure: 24). Twenty-two (69%; acute liver failure: 14) of the 32 patients were alive at onemonth. Presence of HE (p = 0.03) and ∆MELD (p < 0.001) were significant predictors on univariate analysis, while ∆MELD (aOR = 0.88, 95% CI: 0.79-0.98, p = 0.01) was the only significant independentpredictor of one-month transplant-free survival. Area under receiver operating characteristic (ROC) for ∆MELD was 0.93 (95% CI:0.85-1.00) and a decrease of 20% in MELD score while on PLEX-LV had 90% sensitivity and 90% specificity in predicting one-month survival. Decline in MELD while on PLEX-LV independently predicted one-month transplant-free survival in rodenticidal hepatotoxicity patients. This may help guide decision on stopping PLEX-LV in patients predicted to respond to treatment and to consider alternate treatment options in non-responders.

Association of thrombotic microangiopathy with interferon therapy for hepatitis B: a case report

BackgroundThrombotic microangiopathy is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ injury. The pathological features include vascular damage that is manifested by arteriolar and capillary thrombosis with characteristic abnormalities in the endothelium and vessel wall. Thrombocytopenia is one of the common adverse effects of interferon therapy. However, a more serious but rare side effect is thrombotic microangiopathy.Case presentationWe report the case of a 36-year-old Asian male patient with clinical manifestations of hypertension, blurred vision, acute renal failure, thrombocytopenia, and thrombotic microangiopathy. Renal biopsy showed interstitial edema with fibrosis, arteriolar thickening with vitreous changes, and epithelial podocytes segmental fusion. Immunofluorescence microscopy showed C3(+), Ig A(+) deposition in the mesangial region, which was pathologically consistent with thrombotic microangiopathy renal injury and Ig A deposition. The patient had a history of hepatitis B virus infection for more than 5 years. Lamivudine was used in the past, but the injection of long-acting interferon combined with tenofovir alafenamide fumarate was used since 2018. The comprehensive clinical investigation and laboratory examination diagnosed the condition as thrombotic microangiopathy kidney injury caused by interferon. After stopping interferon in his treatment, the patient’s renal function partially recovered after three consecutive therapeutic plasma exchange treatments and follow-up treatment without immunosuppressant. The renal function of the patient remained stable.ConclusionsThis report indicates that interferon can induce thrombotic microangiopathy with acute renal injury, which can progress to chronic renal insufficiency.

A case of hyperviscosity syndrome associated with Waldenström macroglobulinemia treated with membrane plasma exchange without predilution.

A 75-year-old man with blurred vision and nasal bleeding was diagnosed with hyperviscosity syndrome and central retinal vein occlusion secondary to Waldenström macroglobulinemia. Serum total protein and IgM levels were undetectable. Because of the severe symptoms, we determined that immediate plasma-exchange treatment was required to decrease the blood viscosity. The initial plasma exchange was performed using the membrane isolation method with a predilution standby. A saline predilution replacement was prepared to decrease the total membrane pressure (TMP); however, the predilution protocol was not used because the planned treatment volume could be achieved without increasing the TMP. After two consecutive days of membrane plasma exchange, all serum biochemical tests were measurable, and IgM was below 4000mg/dL. After chemotherapy, his visual symptoms improved, and he was discharged. Since it is difficult to assess the risk of elevated TMP prior to initial plasma exchange, membrane plasma exchange with a predilution standby may be a useful strategy for initial plasma exchange for hyperviscosity syndrome in terms of safety and efficiency.

A Randomized Trial Comparing Imlifidase to Plasmapheresis in Kidney Transplant Recipients With Antibody-Mediated Rejection.

Antibody-mediated rejection (ABMR) poses a barrier to long-term graft survival and is one of the most challenging events after kidney transplantation. Removing donor specific antibodies (DSA) through therapeutic plasma exchange (PLEX) is a cornerstone of antibody depletion but has inconsistent effects. Imlifidase is a treatment currently utilized for desensitization with near-complete inactivation of DSA both in the intra- and extravascular space. This was a 6-month, randomized, open-label, multicenter, multinational trial conducted at 14 transplant centers. Thirty patients were randomized to either imlifidase or PLEX treatment. The primary endpoint was reduction in DSA level during the 5 days following the start of treatment. Despite considerable heterogeneity in the trial population, DSA reduction as defined by the primary endpoint was 97% for imlifidase compared to 42% for PLEX. Additionally, imlifidase reduced DSA to noncomplement fixing levels, whereas PLEX failed to do so. After antibody rebound in the imlifidase arm (circa days 6-12), both arms had similar reductions in DSA. Five allograft losses occurred during the 6 months following the start of ABMR treatment-four within the imlifidase arm (18 patients treated) and one in the PLEX arm (10 patients treated). In terms of clinical efficacy, the Kaplan-Meier estimated graft survival was 78% for imlifidase and 89% for PLEX, with a slightly higher eGFR in the PLEX arm at the end of the trial. The observed adverse events in the trial were as expected, and there were no apparent differences between the arms. Imlifidase was safe and well-tolerated in the ABMR population. Despite meeting the primary endpoint of maximum DSA reduction compared to PLEX, the trial was unsuccessful in demonstrating a clinical benefit of imlifidase in this heterogenous ABMR population. EudraCT number: 2018-000022-66, 2020-004777-49; ClinicalTrials.gov identifier: NCT03897205, NCT04711850.

Visual Function Improvement after Plasma Exchange Therapy for Acute Optic Neuritis in Neuromyelitis Optica Spectrum Disorders: Case Series and Review.

Neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorder (NMOSD) are autoimmune-mediated central nervous system disorders distinguished by the presence of serum aquaporine-4 IgG antibody (AQP4-Ab). The clinical panel comprises severe optic neuritis (ON) and transverse myelitis, which can result in incomplete recovery and a high risk of recurrence. This study aimed to evaluate the visual outcomes of three patients with severe acute ON in NMOSD that was non-responsive to intravenous methylprednisolone (IVMP), who received plasma exchange therapy (PLEX). We included three patients (P1, P2 and P3) with severe acute ON who had no improvement after IVMP treatment and were admitted to the ophthalmology department at the Emergency University Hospital Bucharest from January 2022 to September 2023. All three patients with ON were diagnosed in accordance with the criteria described by the Optic Neuritis Treatment Trial. All the subjects were experiencing their first attack. The mean recruitment age was 35.3 ± 7.71. All patients were seropositive for the AQP4 antibody. All patients were tested for serum myelin oligodendrocyte glycoprotein (MOG) antibody but only one showed a positive test (P3). Lesions visible in orbital MRI indicated the involvement of retrobulbar, canalicular and/or intracranial segments. All three subjects had no response or incomplete remission after an IVMP protocol (5 days of 1000 mg intravenous methylprednisolone in sodium chloride 0.9%). The mean time from onset of optic neuritis to PLEX was 37.6 days. The PLEX treatment protocol comprised five cycles of plasma exchange treatment over 10 days, with a plasma exchange session every other day. An amount of 1 to 1.5 volumes of circulating plasma were dialyzed for 2-4 h. At 1 month after the completion of PLEX therapy, BCVA and VF parameters were improved in all three patients. The treatment of ON remains subject to debate and is somewhat controversial. Plasma exchange must be considered as a rescue therapy when IVMP is insufficient for AQP4-ON patients. This study revealed that PLEX treatment effectively improves the visual outcomes of patients experiencing their first attack of severe acute isolated ON after high-dose IVMP treatment. This study suggests that PLEX may be associated with improved visual outcomes in NMOSD acute optic neuritis.

Anti-CFH-associated hemolytic uremic syndrome: do we still need plasma exchange?

Between 5 and 50% of atypical hemolytic uremic syndrome (aHUS) cases in children are caused by autoantibodies against complement factor H (CFH). Given the acquired autoimmune nature of the disease, plasma exchange (PE) and various immunosuppressive treatments have been used. More recently, eculizumab has been proposed. In this multicenter, retrospective study, we report outcomes of 12 children with anti-FH antibody-associated HUS treated with eculizumab associated with various immunosuppressive regimens. Patients were treated with eculizumab for 15.5 [9.5;23.0] months and 3 received PE or IgG adsorption. Three patients received mycophenolate mofetil (MMF) alone, 1 patient received MMF and steroids, 1 patient received MMF and rituximab, 3 patients received MMF/steroids and rituximab, and 4 patients did not receive any immunosuppression. Anti-FH antibody levels significantly decreased but no difference was observed based on the immunosuppressive regimen. Eculizumab was discontinued in 7/10 patients after 11 [7.5;15.5] months and MMF in 6/8 patients after 36 [35;40] months. Anti-FH titers at MMF discontinuation ranged from 257 to 3425 UI/L. None of these patients relapsed and eGFR at last follow-up was above 70mL/min/1.73 m2 in all patients. Eculizumab is effective and safe in inducing and maintaining remission in aHUS secondary to anti-FH antibodies and renders reduction of anti-FH titers less urgent. Anti-FH antibody titers decreased in most patients irrespective of the immunosuppressive treatment chosen, so that a strategy consisting of combining eculizumab with MMF monotherapy seems sufficient at least in non-Indian or less severe forms of anti-FH antibody-associated HUS.

Role of therapeutic plasma exchange in treatment of the hypertriglyceridemia-induced acute pancreatitis: Case report and literature review

Abstract: Hypertriglyceridemia-induced acute pancreatitis (HTG-AP) is associated with a more severe clinical course than acute pancreatitis due to other etiologies. Presently, these patients are managed with dietary restrictions, analgesia, lipid-lowering agents, insulin/heparin dual therapy, and supportive care to prevent organ failure. Apart from these conventional therapies, therapeutic plasma exchange (TPE) is another potential treatment that is being performed as it results in rapid reduction in serum triglycerides and inflammatory cytokines, thus, leading to drastic improvements in clinical and laboratory findings and patient outcomes. Here, we report our experience of using TPE for HTG-AP in our patients.

A rare manifestation presenting as acute pancreatitis of thrombotic thrombocytopenic purpura

AbstractThrombotic thrombocytopenic purpura (TTP) is an unusual disease with a 90% mortality rate without prompt management. The typical clinical manifestations include thrombocytopenia, hemolytic anemia, neurological symptoms, fever, and renal impairment. However, recognizing TTP in its early stages is not always easy due to limited clinical experience and sometimes atypical presentation. We report a 44‐year‐old male who initially suffered from jaundice and skin purpura, followed by epigastric pain. Acute pancreatitis was first suspected after a computerized tomography (CT) scan in the local medical department, without a definite etiology. He was then transferred to our hospital for further investigation of hemolysis. Transient neurological symptoms occurred 1 week after transferring. TTP was later confirmed based on schistocytes noted in peripheral blood smear and ADAMTS‐13 activity = 0%. The patient was discharged successfully after prompt therapeutic plasma exchange and steroid treatment. We present the first case of TTP inducing acute pancreatitis in Asia and remind that acute pancreatitis is a possible cause of abdominal pain, although it's a rare manifestation of TTP.

Relevance of histopathological findings for predictive scoring of short-term treatment response to plasma exchange in severe ANCA-associated renal vasculitides.

Rapidly progressive glomerulonephritis (RPGN) is characterized by a rapid loss of kidney function, affecting both renal and overall patient survival. Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a small vessel vasculitis affecting multiple organ systems including the kidney, and among most frequent causes of RPGN. We here aimed to validate a recently described scoring system for short-term treatment response to therapeutic plasma exchange (PLEX) in a well-characterized and independent cohort of severe renal AAV presenting with RPGN. Furthermore, we compared this scoring with established classification systems in renal AAV including histopathological findings. We here directly compare the scoring system with retrospective data about PLEX treatment in our own clinical practice and according to current recommendations in a cohort of 53 patients with severe AAV presenting with RPGN confirmed by kidney biopsy. We here confirm that PLEX scoring is capable to identify patients at risk for short-term poor outcome in severe AAV presenting with RPGN (p<0.0001). Furthermore, multiple stepwise regression analysis revealed that the PLEX score with renal biopsy performed best to predict poor outcome in this patient population (p<0.0001). Our observations underscore the relevance of performing a kidney biopsy in this patient population that is often challenged in the setting of intensive care treatment, requirement of KRT with need for anticoagulation and bleeding risk. Therefore, validation of our observations and this recent scoring system for treatment response to PLEX in independent cohorts would be of great clinical relevance in the treatment of patients with severe AAV presenting with RPGN.

Early Initiation of Plasma Exchange Therapy for Anti-MDA5+Dermatomyositis with Refractory Rapidly Progressive Interstitial Lung Disease.

Objectives Dermatomyositis (DM) is often associated with fatal anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive rapidly progressive interstitial lung disease (RP-ILD). RP-ILD often fails to respond to intensive treatment and has a poor prognosis. We examined the effectiveness of early plasma exchange therapy plus intensive treatment with high-dose corticosteroids and multiple immunosuppressants. Methods Autoantibodies were identified by an immunoprecipitation assay and enzyme-linked immunosorbent assay. All clinical and immunological data were collected retrospectively from medical charts. We divided patients into two groups based on treatment regimen: intensive immunosuppressive therapy alone as initial treatment (IS group) and early initiation of plasma exchange (PE) plus intensive immunosuppressive therapy (ePE group). Early PE therapy was designated if PE therapy was initiated within two weeks of starting treatment. Comparisons of the treatment response and prognosis between groups were performed. Patients Anti-MDA5-positive DM with RP-ILD was screened. Results Forty-four RP-ILD and DM patients had anti-MDA5 antibodies. Four patients were excluded because they died before receiving sufficient combined immunosuppressive therapy or before the evaluation of the immunosuppressive treatment effectiveness (IS, n=31; ePE, n=9). All 9 patients in the ePE group had improved respiratory symptoms and were alive, whereas 12 of 31 patients in the IS group died (100 vs. 61%, p=0.037). Of the 8 patients who had 2 values for a poor prognosis, indicating the highest risk for death using the MCK model, 3 of 3 patients in the ePE group and 2 of 5 in the IS group were alive (100 vs. 40%, p=0.20). Conclusion The early initiation of ePE therapy plus intensive immunosuppressive therapy was effective for patients with DM and refractory RP-ILD.

Comparison of efficacy and safety of different anticoagulation regimens in plasma exchange: A systematic review and meta-analysis.

Extracorporeal line clotting during plasma exchange (PE) not only delays efficient treatment, but also cause great waste of nursing resources. There is a lack of comprehensive comparison of the efficacy and safety among different anticoagulation regimens in plasma exchange in literature. A systematic search was performed in EMBASE, MEDLINE via PubMed, Cochrane Central Library, and CNKI. Studies that had compared at least two anticoagulation regimens in PE were considered eligible. The anticoagulative efficacy outcome was assessed by the occurrence of extracorporeal circuit clotting. The safety outcome was assessed by the occurrence of bleeding events, post-treatment APTT values, and post-treatment platelets counts. The risk of bias was assessed by the AHRQ tool. Mean differences or standardized mean differences with 95% confidence intervals (CIs) of continuous variables and risk ratios (RRs) with 95% CIs of categorical variables were pooled using a random-effects or a fixed-effects model as appropriate. In all, 7 studies with 1638 patients and 10951 sessions of PE treatment were included. Pooled results indicated the anticoagulative efficacy of UFH was better than that of saline flushing, yet did not differ with those of LMWH or RCA. Although the occurrence of bleeding events had no difference among different pairs of anticoagulation regimens, anticoagulation using UFH might lead to longer post-treatment APTT value and lower post-treatment platelet counts. Only one study was judged to have low risk of bias in each of the five domains in the AHRQ tool. The current anticoagulation regimens are generally effective and well tolerated in PE; however, the number of included studies was too limited to draw definitive conclusions.

A successful plasma exchange inbridging to rituximab forsevere neuropsychiatric lupus andlupus nephritis with viral infections andaspiration pneumonia.

Systematic lupus erythematosus (SLE) is a chronic autoimmune disease involving several organs such as the kidneys, skin, vessels, and central nervous system. Neuropsychiatric SLE (NPSLE) is a life-threatening condition that needs treatment with the combination of glucocorticoids and Immunosuppressants (IS). This includes cyclophosphamide and rituximab (RTX) which can lead to several infections. Therapeutic apheresis is an optional treatment for inflammatory diseases and has less risks of infections than IS. Plasma exchange (PE) is one of the most common apheresis, and is recommended for the management of NPSLE. We report a refractory NPSLE case with bacterial pneumonia and cytomegalovirus antigenemia. PE was performed prior to RTX. After the initiation of RTX which was incompatible due to infection such as aspiration pneumonia and cytomegalic virus, PE was scheduled considering the pharmacokinetics of RTX. Her SLE activity was well managed after PE and RTX without flare. PE treatment plan bridging to IS and RTX may effectively work in refractory SLE patients with infections.

Unmet Needs of Immune Thrombotic Thrombocytopenic Purpura (iTTP)-Specific Pregnancy Counseling, Care and Outcomes in Women with Ittp

Unmet needs of iTTP-specific pregnancy counseling, care and outcomes in women with iTTP INTRODUCTION: Pregnancy is a known trigger for an initial episode or relapse of immune thrombotic thrombocytopenic purpura (iTTP) and outcomes of pregnancy in women with iTTP have historically been suboptimal with high rates of recurrent iTTP, fetal loss, preeclampsia and HELLP syndrome. More recent data suggest that prophylactic immunosuppression to normalize ADAMTS13 levels before conception, and ADAMTS13 monitoring and prophylactic steroids or plasma exchange during pregnancy can improve maternal and fetal outcomes. However, it is not clear whether women with iTTP are routinely counseled regarding these options. We conducted this study to understand the experiences of women with iTTP with reproductive healthcare, how iTTP has impacted their reproductive decisions, and outcomes of pregnancy. METHODS: We developed a web-based (RedCap) survey focused on the reproductive healthcare experiences of women with iTTP with in three major sections: (1) counseling and education around pregnancy that was provided to them, (2) the impact of iTTP on their reproductive decisions, and (3) outcomes of any pregnancies they had experienced. The survey was distributed through social media and email mailing lists of a patient advocacy organization and was kept open for one month (January 2023). Survey data were summarized using counts and percentages. The focus of the analysis was to identify gaps in patient education and care where efforts could be focused on educating clinicians or providing information to patients though patient advocacy groups. RESULTS: Seventy-five females with iTTP responded to the survey. The median age of the respondents was 44 years (range 23 - 65). Sixty-five (74.7%) identified as White, 13 (14.9%) as Black, 6 (6.9%) as Asian and 3 (3.4%) identified as other/prefer not to say. Nearly all (94.6%) were followed by a hematologist or hematologist-oncologist and 82.9% reported being monitored regularly for iTTP. Only 26.7% (20 of 75) reported that their doctor talked to them about measures that may help achieve a successful pregnancy. These included ADAMTS13 monitoring (n=15), plasma exchange treatments (n=10), rituximab (n=10), and aspirin (n=3) (options are not mutually exclusive so total is &amp;gt; 20). Moreover, 30.0% (21 of 70) reported that they were advised by their doctor to not get pregnant due to their iTTP. Some patients (36.0%) avoided pregnancy out of fear of the consequences of iTTP and 28.4% (21 of 74) responded that their iTTP diagnosis has affected their ability to get into a relationship, which impacts their quality of life (Figure 1). Fifty-three patients reported that they had had at least one pregnancy. Of these, 35 had pregnancies before iTTP diagnosis, 10 with the initial presentation of iTTP, and 8 women had a total of 11 pregnancies following the diagnosis of iTTP. Consistent with prior reports, there was a high rate of maternal and fetal complications in pregnancies that occurred in the setting of a first iTTP episode complicating pregnancy, or pregnancies after an iTTP diagnosis (Table 1). iTTP relapse occurred in 27.3% (3 of 11) pregnancies in women with prior iTTP. Fetal loss occurred in 30% of pregnancies with first TTP diagnosis and 9% of pregnancies after iTTP. In both groups, approximately 20% were small for gestational age. Preeclampsia or HELLP syndrome occurred in 50% and 18.2% of pregnancies complicated by initial TTP diagnosis or after iTTP diagnosis, respectively. CONCLUSION: Though pregnancy in women with iTTP is high risk, close monitoring and prophylactic interventions can improve outcomes. While many women with iTTP are counseled regarding the risks of pregnancy, few receive counseling regarding their options to potentially improve pregnancy outcomes. This limits their reproductive choices and impacts their relationships. Educating clinicians and providing information to patients though patient advocacy groups may help address these healthcare gaps.

Caplacizumab for immune thrombotic thrombocytopenic purpura: real-world multicenter data.

Given the limited real-world data of caplacizumab, our multicenter real-world study was designed to assess the safety and efficacy of caplacizumab in immune thrombotic thrombocytopenic pupura (iTTP), compared to historic controls. We have studied 70 patients: 23 in the caplacizumab and 47 in the historic control group. Plasma exchange was applied in all episodes except for two patients that denied plasma exchange. Rituximab as first-line treatment was more common in the caplacizumab group compared to historic control. Caplacizumab (10 mg daily) was given at a median on day 7 (1-43) from initial diagnosis for 32 (6-47) dosages. In the caplacizumab group, a median of 12 (8-23) patients required plasma exchange sessions versus 14 (6-32) in the control group. Caplacizumab administration did not produce any grade 3 complications or major hemorrhagic events. After a median of 19.0 (2.6-320) months since the iTTP diagnosis, 5 deaths occurred (4 in the control group and 1 in the caplacizumab group, p = 0.310). Caplacizumab patients achieved early platelet normalization and ADAMTS13 activity normalization at the end of treatment. Relapse was observed only in 2/23 (9%) caplacizumab patients, compared to 29/47 (62%) historic controls (p < 0.001). Overall, caplacizumab is safe and effective in treating iTTP, including cases refractory to plasma exchange, re-administration, and cases without previous plasma exchange treatment. No major hemorrhagic events were observed. Cessation of dosing guided by ADAMTS13 has ensured a low relapse rate.